The purpose of this study is to test the efficacy of a uniquely targeted HIV risk reduction intervention for young transgender women (YTW), ages 16 to 24, at risk for HIV acquisition or transmission. Evidence indicates that transgender women have HIV prevalence rates as high as or higher than other high risk groups (i.e., >25%), compounded by a startling rate of unrecognized infection (i.e., >10%), with the largest percentage among YTW (ages 29 and younger). High rates of risky sexual behavior and HIV infection among this population of young women indicate a need for comprehensive HIV prevention programs targeted to their unique circumstances. A prior CDC-funded pilot study conducted by the study team suggests that intervening among this group is feasible, acceptable, and efficacious. In 2008-2009, members of the target population (i.e., YTW), with guidance from a multidisciplinary research team, led the development of a holistic, theoretically-driven intervention curriculum (i.e., "Life Skills") grounded in the social realities of YTW. We found that enrollment and retention of the study population was feasible (i.e., 51 participants enrolled in 6 months) and both retention and session attendance were high (84% retained over the course of the study). We propose to test this intervention in a three-arm randomized controlled trial in two major U.S. cities with excellent access to and research experience with the population. We will enroll 375 at risk YTW, ages 16-24;two-fifths of the sample (N=150) randomized to the intervention will participate in the 6-session group-based and manualized Life Skills intervention;two-fifths (N=150) will be randomized to the standard-of-care (SOC) control condition;and one- fifth will be randomized to the time-matched attention control condition (N=75) and receive standard health promotion information in a group-based multi-session format. All three arms will receive HIV and STI (Chlamydia and gonorrhea) testing and pre-posttest risk reduction counseling (i.e., SOC). Sexual risk will be assessed at baseline, 4, 8 and 12 months post-intervention Our specific aims are: 1) to determine the efficacy of the Life Skills intervention in comparison to a SOC arm and a time-matched attention control on the primary outcome: number of unprotected anal sex acts (UAS) (in the previous four months) among YTW, ages 16-24;and 2) to examine the degree to which improvements in sexual risk taking are mediated by the conceptual mediators of the intervention: transgender adaptation and integration, collective self-esteem/empowerment, information (HIV knowledge), motivation (attitudes, norms, and intentions for safer sex), and behavioral skills (discussing sex and condom use with sexual partners, acquiring and using condoms);and to explore whether reductions in sexual risk are associated with epidemiologically-linked moderators of sexual risk behavior: age, race/ethnicity, and psychosocial factors. An additional exploratory aim is to describe the prevalence of HIV and STIs in the community recruited sample;in the SOC arm, we will assess the natural trajectory of sexual risk behavior and the acquisition of HIV and STIs (incidence rate) in YTW over a 12-month follow-up period. PUBLIC HEALTH RELEVANCE: High rates of risky sexual behavior and HIV infection among young transgender women indicate a need for comprehensive HIV prevention programs targeted to their unique circumstances. The purpose of this study is to test the efficacy of a uniquely targeted HIV risk reduction intervention for young transgender women (YTW), ages 16 to 24, at risk for HIV acquisition or transmission. Effective interventions to prevent HIV infection in YTW may decrease the population burden of disease.